This was a randomized, double-blinded, placebo-controlled evaluation of the prophylactic antimalarial activity of atovaquone (a broad spectrum antiprotozoal agent). The dosing regimens included atovaquone 750 mg x 7 (6 subjects); atovaquone 250 mg x 1 (6 subjects); and placebo (4 subjects). The study was conducted largely on an outpatient basis. In the fall of 1996, sixteen eligible volunteers received seven daily doses of atovaquone/placebo and were challenged with Plasmodiumfalciparum (by the bite of five infected mosquitoes). They were then monitored for evidence of circulating malaria parasites. Followup continued through the fall of 1997. Of the 654 scheduled outpatient visits, three were missed (99.5% overall compliance), all by a single volunteer for whom the frequent visits posed a hardship. To ensure his safety, he agreed to be admitted to the inpatient GCRC unit, where he was monitored reliably for 54 days.